This project will investigate the efferent pathways, from brain to periphery, through which psychological factors contribute to the expression, severity and management of inflammation in asthma. In addition, it will establish the efficacy of mindfulness-based stress reduction (MBSR) training in reducing the lung function impairment and inflammation associated with exposure the allergen in asthmatic individuals by reducing the reactivity of emotion-related neural circuitry. We will recruit asthmatic individuals with a dual response to allergen exposure, who will be randomized to either MBSR training or to a wait-list control group. Participants will undergo an inhaled allergen challenge and provide measures of pulmonary function and asthma-relevant inflammation pre- and post-intervention. In addition, fMRI data will be collected during the hour preceding the onset of the late-phase response. This timing was designed to detect neural signals that may influence the development inflammation that underiies the late-phase fall in lung function. During fMRI data collection, participants perform a variant of the Stroop Task, where they identify the color of letters spelling asthma- related (e.g. wheeze), generally negative (e.g. loneliness), or neutral (e.g. curtains) words. This design is based on our prior work showing increased activation in affective neural circuitry, specifically to disease- related cues, in the context of allergen challenge. This increased responsivity predicted the lung function decline and inflammation associated with the late-phase response that would occur several hours later. The current design allows up to specifically target the efferent pathways in this bi-directional relationship, by employing an intervention focused on cognitive and emotional processes. In so doing, we have the potential to identify an entirely new domain of disease management strategies, such as neurofeedback, geared at reducing responsivity in specific neural circuits to impact the function of peripheral disease processes. Thus, our proposed project represents a new paradigm in asthma and holds the promise to better understand the complexity of this disease, its regulation, and ultimately to provide for more effective treatment. RELEVANCE (See instructions): Asthma currently represents and enormous public health burden, affecting more than 10% of the population in the U.S., and costing tens of billions of dollars in healthcare and leading to tens of millions of missed days of work. Current treatment strategies are expensive and not fully effective in some individuals. Given the evidence suggesting that psychological factors contribute substantially to asthma symptom expression, an intervention that addresses this influence on asthma exacerbation is missing from the current toolbox.